IMRT-TMI With Fludarabine as Myeloablative Conditioning for Allogeneic HSCT

Last updated on July 2021

Recruitment

Recruitment Status: Active, not recruiting
Estimated Enrollment: 53

Summary

Conditions

Acute Lymphocytic Leukemia
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
Myelodysplastic Syndromes

Type

Interventional

Phase

Phase 1

Design

Allocation: N/AIntervention Model: Sequential AssignmentIntervention Model Description: Standard "3+3" phase I design of dose escalation using 3 patients per dose level cohort with an expansion to 6 patients at the MTD will be used in Phase I. We will treat 3 patients at the initial dose level of TMI. If no dose-limiting toxicity (DLT) is observed, the next cohort of three patients is treated at the next higher dose level. If 1 of the 3 patients demonstrates DLT, an additional 3 patients are treated at that dose level. If only 1 of the 6 shows DLT, the next cohort of three patients is entered at the next dose level. If 2 or more of the 6 demonstrate DLT, the MTD is defined as the previous dose level. If no DLT is observed in the final dose level, the number of patients treated will be expanded to 6. In phase II, we will enroll additional patients at the defined MTD level. *Stopping criteria was met during the first dose level cohort in Phase l. The trial will not continue into Phase II as originally planned.Masking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age: Between 18 years and 65 years
Gender: Both males and females

Description

This is a phase I/II clinical trial to determine the maximum tolerated dose (MTD) of intensity modulated radiation therapy based total marrow irradiation (TMI) concurrent with fludarabine as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (Allo-HSCT), as well as to determine the efficacy of the regimen in patients with high-risk and relapsed or refractory leukemia and myelodysplasia. TMI, which allows for conformal dosing of target bone marrow tissue while giving lower doses to organs at risk, is considered by many to be a superior alternative to conventional total body irradiation (TBI) Primary Objectives: Phase I: Determine the MTD of TMI given concurrently with fludarabine (fixed at 150 mg/m2) as a conditioning regimen for Allo-HSCT for patients with high risk (relapsed/refractory) acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelogenous leukemia (CML). Phase II: Single-arm exploratory study to expand the cohort at the MTD level to estimate 1- year overall survival (OS), with the objective of increasing the OS from the historical rate of 30% (null hypothesis ) to 50% (alternate hypothesis) with 80% power and a one-sided type I error of 0.05. Secondary Objectives Describe the extramedullary toxicity and the incidence of complications, including mucositis, acute and chronic graft versus host disease (GvHD), sinusoidal obstruction syndrome (SOS), and pneumonitis. Describe the time to engraftment of neutrophils and platelets Describe the disease response rate at day 30 after transplantation Describe the overall survival and disease-free survival Describe the cumulative incidence of relapse and non-relapse mortality Determine the correlation between plasma/serum markers and radiation induced acute and long term toxicities. Describe the quality of life metrics of participating subjects Stopping criteria was met during the first dose level cohort in Phase l. The trial will not continue into Phase II as originally planned.

Tracking Information

NCT #: NCT03696537
Collaborators: Indiana University
Investigators: Principal Investigator: Naoyuki G Saito, MD PhD Indiana University